Insights into the mechanism of normal and aberrant hematopoiesis have been provided by the study of patients with bone marrow failure and their tissues. Patients with aplastic anemia have been treated in the Clinical Center with drug immunosuppression consisting of lymphocytophereis, plasmaphesis, cyclophosphamide, and prednisone; the best hematologic responses have been achieved with antithymocyte globulin. Studies of the tissues of patients with aplastic anemia have disclosed and abnormal ratio of helper to suppressor lymphocytes in the peripheral blood, but this ratio remains abnormal even with hematopoietic recovery. It has proven extremely difficult to demonstrate a suppressor lymphocyte using monoclonal antibodies in tissue culture systems. Helper lymphocytes are decreased significantly in aplastic amemia. In additions, natural killer cell function is also dificient, possibly as a result of multiple transfusions. the role of cell-cell interaction in bone marrow failure thus remains uncertain. However, strong, evidence has been developed that in transient aplastic crises that occur in children with sickle cell anemia, the mechanism of suppression is direct infection of bone marrow with a human parvovirus-like agent.